1. Field of the Invention
The embodiments of the invention generally relate to molecular separation methods, and more particularly to macromolecular separation based on differential mobility.
2. Description of the Related Art
In biology and chemistry, there is wide interest in the ability to sort polyelectrolytes and molecules by their length, in particular for deoxyribonucleic acid (DNA) sequencing purposes. The need for genome sequencing and the demand for genetic diagnosis and testing tools for health related applications require high throughput and low cost sequencing methods. Electrophoresis is generally described as the movement of charged molecules, such as proteins in the presence of an electric field. Generally, the separation of molecules in an electric field is based on the size, shape, and charge of a particular molecule. A description of end label free-solution electrophoresis (ELFSE) is provided in Mayer et al., “Theory of DNA Sequencing Using Free-Solution Electrophoresis of Protein-DNA Complexes,” Anal. Chem. 1994, 66, 1777-1780, the complete disclosure of which in its entirety is herein incorporated by reference.
Other conventional electrophoresis techniques generally consist of slab or capillary electrophoresis using dilute or entangled polymers. Although those techniques have been shown to successfully separate fragments with hundreds of bases (i.e., DNA bases—adenine, thymine, guanine, and cytosine) the time required to achieve an efficient separation is a major limitation to the development of high throughput sequencing systems. To increase the mobility of polyelectrolytes in sieving matrixes and, hence, in DNA sequencing speed, higher electric fields are often used. However, these resulting higher velocities and higher electric fields generally lead to a decrease in resolution and a degradation of the sieving medium. Therefore, new physical separation mechanisms are necessary in order to improve throughput by both decreasing the size of the sampled population and increasing the processing speed.